Nonalcoholic fatty liver disease: a potential consequence of tumor necrosis factor-inhibitor therapy.
Nonalcoholic fatty liver disease: a potential consequence of tumor necrosis factor-inhibitor therapy.
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DOI：
10.1097/meg.0000000000000421
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发表时间：
2015-10
影响因子：
2.1
通讯作者：
Brown G
中科院分区：
文献类型：
--
作者：
Feagins LA;Flores A;Arriens C;Park C;Crook T;Reimold A;Brown G
尽管肿瘤坏死因子抑制剂 (TNFi) 有望预防非酒精性脂肪性肝病 (NAFLD)，但我们已经看到患者在 TNFi 治疗期间似乎出现 NAFLD。我们旨在通过病例对照研究探讨这种 TNFi 并发症的危险因素。我们回顾了退伍军人管理局医院的临床记录，以确定在 TNFi 治疗期间出现转氨酶升高以及肝活检显示 NAFLD 的炎症性疾病患者。这些患者与三个对照组的患者进行匹配：(i) 炎症性疾病对照：接受 TNFi 治疗且转氨酶水平正常的患者；(ii) 非酒精性脂肪性肝炎 (NASH) 对照：经活检证实患有 NASH 且无其他炎症性疾病的患者；(iii) 健康对照。对 PNPLA3（一种易患 NASH 的基因）进行了基因分型。我们确定了 8 例（5 例脂肪性肝炎，3 例脂肪变性）；在 TNFi 治疗后 1-63 个月（平均 12 个月）首次观察到转氨酶水平升高。 5 名患者停止了 TNFi 治疗，其转氨酶水平在 2-8 个月内恢复正常。病例和炎症性疾病对照之间代谢综合征特征的频率没有显着差异。病例比炎症对照组有更多的甲氨蝶呤暴露（50% vs. 12.5%，P = 0.28）。 PNPLA3 基因分型显示 75% 的病例、38% 的炎症对照、88% 的 NASH 对照和 63% 的健康对照存在突变 (P= NS)。我们的研究结果表明，NAFLD 可能是 TNFi 治疗的副作用，而甲氨蝶呤暴露和 PNPLA3 基因突变可能是危险因素。需要进一步的研究来确定 TNFi 如何导致 NAFLD 并确认这些危险因素。
Although tumor necrosis factor inhibitors (TNFi) might be expected to protect against nonalcoholic fatty liver disease (NAFLD), we have seen patients who appeared to develop NAFLD during TNFi treatment. We aimed to explore risk factors for this TNFi complication in a case–control study. We reviewed clinic records at our VA hospital to identify patients with inflammatory diseases who developed aminotransferase elevations during TNFi therapy and who had liver biopsies showing NAFLD. These patients were matched with patients in each of three control groups: (i) inflammatory disease controls: patients on TNFi treatment with normal aminotransferase levels, (ii) nonalcoholic steatohepatitis (NASH) controls: patients with biopsy-proven NASH with no other inflammatory disease, and (iii) healthy controls. Genotyping was performed for PNPLA3, a gene predisposing to NASH. We identified eight cases (five steatohepatitis, three steatosis); elevated aminotransferase levels were first observed 1–63 months into TNFi therapy (average 12 months). TNFi therapy was stopped in five patients, whose aminotransferase levels then normalized within 2–8 months. There were no significant differences between cases and inflammatory disease controls in the frequency of features of metabolic syndrome. Cases had more methotrexate exposure than inflammatory controls (50 vs. 12.5%, P= 0.28). PNPLA3 genotyping revealed mutations in 75% of cases, 38% of inflammatory controls, 88% of NASH controls, and 63% of healthy controls (P= NS). Our findings suggest that NAFLD can be a side effect of TNFi therapy, and that methotrexate exposure and PNPLA3 gene mutations might be risk factors. Further studies are needed to determine how TNFi causes NAFLD and to confirm these risk factors.